Role of the subicular regions of the rat hippocampus on cognitive task performance and cocaine self-administration and reinstatement behavior

There is considerable interest in elucidating the neurocognitive mechanisms of drug abuse. This dissertation investigates hippocampal memory system involvement in cocaine addiction. First, to verify the cognitive functions of the dorsal (dSUB) or ventral (vSUB) subiculum, the primary output regions of the hippocampus, two radial arm maze tasks were examined after lidocaine inactivation of each site (experiments 1--2). Inactivation of the dSUB and vSUB with 10mug lidocaine impaired hippocampal-dependent win-shift performance. These impairments confirm the spatial processing functions of the dSUB and vSUB. Amygdalar-dependent conditioned cue preference was unaffected following inactivation of either site. In experiments 3--5, the role of these cognitively identified sites in regulating addiction-related behaviors (drug-seeking and drug-taking) after long-term exposure to drug and drug-paired cues was examined utilizing contextually discriminable intravenous cocaine self-administration procedures. During the cocaine maintenance phase, inactivation of only the dSUB with 100mug lidocaine significantly reduced drug-taking behavior, suggesting this site regulates certain aspects of cocaine intake. However, during the reinstatement phases, inactivation of neither site influenced drug-seeking behavior induced by presentation of cocaine-paired cues available with or without a cocaine priming injection. As reinstatement testing took place after long-term exposure to drug and drug-paired cues, it is not surprising that inactivation of hippocampal sites was ineffective during reinstatement. The hippocampus is thought to encode and consolidate contextual associations early in the learning process and is less involved in regulating contextually-dependent behavior after these details are consolidated through long-term exposure. Therefore, experiment 6 investigated the impact of vSUB damage prior to initial exposure to cocaine and drug-paired cues. vSUB lesioned rats successfully acquired cocaine self-administration, i.e., they made more lever responses when cocaine was available than when saline was available for self-administration. However, cocaine-paired contextual cues had a reduced ability to reinstate drug-seeking behavior in vSUB lesioned rats compared to sham controls. vSUB lesioned rats also were unable to differentiate between drug- and saline-paired contexts. This investigation implicates the hippocampa memory system in encoding and consolidating the critical relationship between cocaine and the cocaine-associated context that sets the stage for addiction, but suggests minimal involvement in the regulation of long-term relapse-related behaviors.